Long regulatory elements (LREs), such as CpG islands, polydA:dT tracts or AU-rich elements, are thought to play key roles in gene regulation but, as opposed to conventional binding sites of transcription factors, few methods have been proposed to formally and automatically characterize them. We present here a computational approach named DExTER dedicated to the identification of LREs and apply it to the analysis of the genomes of different eukaryotes including P. falciparum. Our analyses show that all tested genomes contain several LREs that are somewhat conserved along evolution, and that gene expression can be predicted with surprising accuracy on the basis of these long regions only. Regulation by LREs exhibits very different behaviours depending on species and conditions. On Apicomplexa organisms, the process appears highly dynamic, with different LREs involved at different phases of their life cycle. For multicellular organisms, the same LREs are involved in all tissues, but a dynamic behavior is observed along embryonic development stages. In P. falciparum, whose genome is known to be strongly depleted of transcription factors, LREs appear to be of especially high importance, and our analyses show that they are involved in both transcriptomic and post-transcriptomic regulation mechanisms. Moreover, we demonstrated the biological relevance of one the LREs discovered by DExTER in P. falciparum using an in vivo reporter assay.

中文翻译：

---

鉴定恶性疟原虫和其他真核生物基因组中的长调控元件

长调控元件（LRE），例如CpG岛，polydA：dT片段或富含AU的元件，被认为在基因调控中起关键作用，但是与传统的转录因子结合位点相反，很少有人提议正式使用这种方法。并自动表征它们。我们在这里提出一种名为DExTER的计算方法，专门用于鉴定LRE，并将其应用于包括恶性疟原虫在内的不同真核生物的基因组分析。我们的分析表明，所有测试的基因组均包含几个在进化中较为保守的LRE，并且仅基于这些长区域，就可以以惊人的准确性预测基因表达。LRE的调节表现出非常不同的行为，具体取决于物种和条件。在Apicomplexa生物上，该过程看起来是高度动态的，在生命周期的不同阶段涉及不同的LRE。对于多细胞生物，所有组织都涉及相同的LRE，但是在胚胎发育阶段会观察到动态行为。在恶性疟原虫中，其基因组被大量消耗转录因子，LRE显得尤为重要，我们的分析表明，它们参与了转录组和转录后调控机制。此外，我们使用体内报告基因试验证明了DExTER在恶性疟原虫中发现的一种LRE的生物学相关性。LRE已知其基因组中的转录因子被大量消耗，因此LRE显得尤为重要，我们的分析表明它们参与了转录组和转录后调控机制。此外，我们使用体内报告基因试验证明了DExTER在恶性疟原虫中发现的一种LRE的生物学相关性。已知LREs的基因组中大量缺少转录因子，因此LRE显得尤为重要，我们的分析表明它们参与了转录组和转录后调控机制。此外，我们使用体内报告基因试验证明了DExTER在恶性疟原虫中发现的一种LRE的生物学相关性。